Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving
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PROVIDER: PRJNA1098628 | ENA |
REPOSITORIES: ENA
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Project description:In the ‘incubation of cocaine craving’ model of relapse, rats self-administer cocaine and then experience a prolonged abstinence period. After this prolonged abstinence period, rats exhibit a progressive intensification (incubation) of cue-induced craving, and the expression of incubated craving depends on plasticity of excitatory synaptic transmission in nucleus accumbens (NAc) core medium spiny neurons (MSN). Previously, we found that the maintenance of this plasticity depends on ongoing protein translation, and that regulation of translation is altered after incubation of cocaine craving. Here we used male and female rats that express Cre recombinase in either dopamine D1 receptor- or adenosine 2a (A2a) receptor-expressing MSN to express a GFP-tagged ribosomal protein in a cell-type specific manner, enabling us to use Translating Ribosome Affinity Purification (TRAP) to isolate actively translating mRNAs from both MSN subtypes for analysis by RNA-Seq. We compared rats that self-administered saline or cocaine. Saline rats were assessed on abstinence day (AD) 1, while cocaine rats were assessed on AD1 or AD40-50. For both D1 and A2a MSN, there were few differentially translated (DT) genes between saline and cocaine AD1 groups. In contrast, a pronounced divergence was observed between cocaine rats on AD1 and AD40, and this was far more robust in D1 MSN. Finally, all comparisons revealed sex differences in translating mRNAs. This study, the first to combine TRAP-seq, transgenic rats, and a cocaine self-administration paradigm, identifies translating mRNAs specifically linked to incubation of cocaine craving in D1 and A2a MSN of the NAc core.
2025-04-29 | GSE263646 | GEO
Project description:In the 'incubation of cocaine craving' model of relapse, rats exhibit progressive intensification (incubation) of cue-induced craving over several weeks of forced abstinence from cocaine self-administration. The expression of incubated craving depends on plasticity of excitatory synaptic transmission in nucleus accumbens core (NAcC) medium spiny neurons (MSN). Previously, we found that the maintenance of this plasticity and the expression of incubation depends on ongoing protein translation, and the regulation of translation is altered after incubation of cocaine craving. Here we used male and female rats that express Cre recombinase in either dopamine D1 receptor- or adenosine 2a (A2a) receptor-expressing MSN to express a GFP-tagged ribosomal protein in a cell-type specific manner, enabling us to use Translating Ribosome Affinity Purification (TRAP) to isolate actively translating mRNAs from both MSN subtypes for analysis by RNA-seq. We compared rats that self-administered saline or cocaine. Saline rats were assessed on abstinence day (AD) 1, while cocaine rats were assessed on AD1 or AD40-50. For both D1-MSN and A2a-MSN, there were few differentially translated genes between saline and cocaine AD1 groups. In contrast, pronounced differences in the translatome were observed between cocaine rats on AD1 and AD40-50, and this was far more robust in D1-MSN. Notably, all comparisons revealed sex differences in translating mRNAs. Sequencing results were validated by qRT-PCR for several genes of interest. This study, the first to combine TRAP-seq, transgenic rats, and a cocaine self-administration paradigm, identifies translating mRNAs linked to incubation of cocaine craving in D1-MSN and A2a-MSN of the NAcC.
| S-EPMC11429699 | biostudies-literature
Project description:Neuroadaptations in the nucleus accumbens (NAc) underlie cue-induced cocaine craving that intensifies (“incubates”) during withdrawal and contributes to persistent relapse vulnerability. Long-lasting gene changes govern perpetual behavioral abnormalities but the role of epigenetic plasticity in cocaine craving during prolonged withdrawal is poorly understood. Here we show that chromatin remodeler INO80 in the NAc mediates cocaine-induced, withdrawal-dependent plasticity and incubated cocaine craving.
2019-10-29 | GSE119627 | GEO
Project description:Gene expression profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests.
2015-02-27 | GSE66349 | GEO
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests.
2015-02-27 | GSE66348 | GEO
Project description:Gene expression profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests. The groups consist of 1. Saline rats (Sal.) 2. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day (1W) 3. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day and to an extinction test for assessment of cue-induced cocaine-seeking behavior (1C) 4. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days (30W) 5. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days and to an extinction test for assessment of cue-induced cocaine-seeking behavior (30C)
2015-02-27 | E-GEOD-66349 | biostudies-arrayexpress
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests. The groups consist of 1. Saline rats (Sal.) 2. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day (1W) 3. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day and to an extinction test for assessment of cue-induced cocaine-seeking behavior (1C) 4. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days (30W) 5. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days and to an extinction test for assessment of cue-induced cocaine-seeking behavior (30C)
2015-02-27 | E-GEOD-66348 | biostudies-arrayexpress
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine, were subjected to 30 withdrawal days, were treated with aCSF, RG108 or SAM and were subjected to extinction tests. The groups consist of: 1. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with aCSF and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (aCSF) 2. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with RG108 and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (RG108) 3. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with SAM and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (SAM)
2015-02-27 | E-GEOD-66347 | biostudies-arrayexpress
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine, were subjected to 30 withdrawal days, were treated with aCSF, RG108 or SAM and were subjected to extinction tests.
2015-02-27 | GSE66347 | GEO
Project description:Dopamine (DA) signaling plays an essential role in reward valence attribution and in encoding the reinforcing properties of natural and artificial rewards. The adaptive responses from midbrain dopamine neurons to artificial rewards such as drugs of abuse are therefore important for understanding the development of substance use disorders. Drug-induced changes in gene expression are one such adaptation that can determine the activity of dopamine signaling in projection regions of the brain reward system. One of the major challenges to obtaining this understanding is the inherent cellular heterogeneity in the brain, where each neuron population can be defined by a distinct transcriptional profile. To bridge this gap, we have adapted a virus-based method for labeling and capture of dopamine nuclei, coupled with nuclear RNA-sequencing and bioinformatics analyses, to study the transcriptional adaptations, specifically, of dopamine neurons in the ventral tegmental area (VTA) during cocaine taking and cocaine craving, using a mouse model of cocaine intravenous self-administration (IVSA). Our results show significant changes in gene expression across non-drug operant training, cocaine taking, and cocaine craving, highlighted by an enrichment in expression of repressive epigenetic modifying enzymes during cocaine craving. Immunohistochemical validation further revealed an increase of H3K9me3 deposition in DA neurons during cocaine craving. These results demonstrate that cocaine-induced transcriptional adaptations in dopamine neurons vary by phase of self-administration and suggest that such an approach may be useful in identifying relevant phase-specific molecular targets to alter the behavioral course of substance use disorders.
2024-11-22 | GSE277757 | GEO